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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
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A functional analysis of differentially expressed microRNAs involved in liver injury in mice with autoimmune hepatitis induced by concanavalin A

DOI: 10.3969/j.issn.1001-5256.2021.06.028
  • Received Date: 2020-11-27
  • Accepted Date: 2020-12-25
  • Published Date: 2021-06-20
  •   Objective  To investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA).  Methods  Eight healthy male specific pathogen-free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t-test was used for comparison of differentially expressed miRNAs between two groups.  Results  The principal component analysis showed that the inter-group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as "DNA binding" (P=1.47×10-6), participated in the biological processes such as "transcription, DNA-templated" (P=2.36×10-7), and were mainly enriched in the cellular components such as "neuronal cell body" (P=5.99×10-6), while the target genes of the downregulated miRNAs had the molecular functions such as "RNA polymerase Ⅱ proximal promoter sequence-specific DNA binding" (P=2.49×10-6), participated in the biological processes such as "regulation of transcription, DNA-templated" (P=1.64×10-11), and were mainly enriched in the cellular components such as "nucleoplasm" (P=4.30×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in "Endocytosis" (P=0.000 4), while the target genes of the downregulated miRNAs were mainly enriched in the "Hippo signaling pathway" (P=0.004), and the above functional analysis results were statistically significant (P < 0.05).  Conclusion  There are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH.

     

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  • [1]
    KRAWITT EL. Autoimmune hepatitis[J]. N Engl J Med, 2006, 354(1): 54-66. DOI: 10.1056/NEJMra050408.
    [2]
    PAPE S, SCHRAMM C, GEVERS TJ. Clinical management of autoimmune hepatitis[J]. United European Gastroenterol J, 2019, 7(9): 1156-1163. DOI: 10.1177/2050640619872408.
    [3]
    FRANCQUE S, VONGHIA L, RAMON A, et al. Epidemiology and treatment of autoimmune hepatitis[J]. Hepat Med, 2012, 4: 1-10. DOI: 10.2147/HMER.S16321.
    [4]
    LOOSEN SH, SCHUELLER F, TRAUTWEIN C, et al. Role of circulating microRNAs in liver diseases[J]. World J Hepatol, 2017, 9(12): 586-594. DOI: 10.4254/wjh.v9.i12.586.
    [5]
    HAO JH, CHEN H, GAO Y, et al. Effects of Saikosaponin d on differentially expressed genes CTLA-4, IL-10 and IL-17 in mice with autoimmune hepatitis[J]. J Shanghai Jiaotong Univ (Med Sci), 2020, 40(3): 303-309. DOI: 10.3969/j.issn.1674-8115.2020.03.005.

    郝健亨, 陈浩, 高艳, 等. 柴胡皂苷d对自身免疫性肝炎小鼠差异表达基因CTLA-4、IL-10和IL-17的影响[J]. 上海交通大学学报(医学版), 2020, 40(3): 303-309. DOI: 10.3969/j.issn.1674-8115.2020.03.005.
    [6]
    CHEN H, HAO JH, LI ZC, et al. Screening for differentially expressed genes in mice with autoimmune hepatitis and effect of saikosaponin-D on the expression of several differentially expressed genes[J]. J Clin Hepatol, 2020, 36(4): 840-846. DOI: 10.3969/j.issn.1001-5256.2020.04.026.

    陈浩, 郝健亨, 李振城, 等. 自身免疫性肝炎小鼠模型差异表达基因的筛查及柴胡皂苷D对部分差异表达基因表达的影响[J]. 临床肝胆病杂志, 2020, 36(4): 840-846. DOI: 10.3969/j.issn.1001-5256.2020.04.026.
    [7]
    LIU Y, CHEN H, HAO JH, et al. Characterization and functional prediction of the microRNAs differentially expressed in a mouse model of concanavalin a-induced autoimmune hepatitis[J]. Int J Med Sci, 2020, 17(15): 2312-2327. DOI: 10.7150/ijms.47766.
    [8]
    SUCHER E, SUCHER R, GRADISTANAC T, et al. Autoimmune hepatitis-immunologically triggered liver pathogenesis-diagnostic and therapeutic strategies[J]. J Immunol Res, 2019, 2019: 9437043. DOI: 10.1155/2019/9437043.
    [9]
    THAN NN, JEFFERY HC, OO YH. Autoimmune hepatitis: Progress from global immunosuppression to personalised regulatory T cell therapy[J]. Can J Gastroenterol Hepatol, 2016, 2016: 7181685. Doi: 10.1155/2016/7181685.
    [10]
    HAYES CN, CHAYAMA K. MicroRNAs as biomarkers for liver disease and hepatocellular carcinoma[J]. Int J Mol Sci, 2016, 17(3): 280. DOI: 10.3390/ijms17030280.
    [11]
    LU FB, CHEN DZ, CHEN L, et al. Attenuation of experimental autoimmune hepatitis in mice with bone mesenchymal stem cell-derived exosomes carrying microRNA-223-3p[J]. Mol Cells, 2019, 42(12): 906-918. DOI: 10.14348/molcells.2019.2283.
    [12]
    BLAYA D, AGUILAR-BRAVO B, HAO F, et al. Expression of microRNA-155 in inflammatory cells modulates liver injury[J]. Hepatology, 2018, 68(2): 691-706. DOI: 10.1002/hep.29833.
    [13]
    SUI C, ZHANG L, HU Y. MicroRNA-let-7a inhibition inhibits LPS?induced inflammatory injury of chondrocytes by targeting IL6R[J]. Mol Med Rep, 20(3): 2633-2640. DOI: 10.3892/mmr.2019.10493.
    [14]
    RUSSELL JO, MONGA SP. Wnt/β-catenin signaling in liver development, homeostasis, and pathobiology[J]. Annu Rev Pathol, 2018, 13: 351-378. DOI: 10.1146/annurev-pathol-020117-044010.
    [15]
    ZHOU D, YU Y, AN Y, et al. EGCG mediated Wnt/β-catenin signaling pathway improves liver damage in mice with immune hepatitis[J]. Anatomy Res 2020, 42 (1): 38-43. DOI: GDJP.0.2020-01-007

    周丹, 于洋, 安洋, 等. 表没食子儿茶素没食子酸酯通过Wnt/β-catenin信号通路改善免疫性肝炎小鼠肝损伤[J]. 解剖学研究, 2020, 42(1): 38-43. DOI: GDJP.0.2020-01-007.
    [16]
    ZHAO L, JIN Y, DONAHUE K, et al. Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling[J]. Hepatology, 2019, 69(6): 2623-2635. DOI: 10.1002/hep.30563.
    [17]
    SONG H, DU C, WANG X, et al. MicroRNA-101 inhibits autophagy to alleviate liver ischemia/reperfusion injury via regulating the mTOR signaling pathway[J]. Int J Mol Med, 2019, 43(3): 1331-1342. DOI: 10.3892/ijmm.2019.4077.
    [18]
    LEI Y, WANG QL, SHEN L, et al. MicroRNA-101 suppresses liver fibrosis by downregulating PI3K/Akt/mTOR signaling pathway[J]. Clin Res Hepatol Gastroenterol, 2019, 43(5): 575-584. DOI: 10.1016/j.clinre.2019.02.003.
    [19]
    SZEKERCZÉS T, GÓGL A, ILLYÉS I, et al. Autophagy, mitophagy and microRNA expression in chronic hepatitis C and autoimmune hepatitis[J]. Pathol Oncol Res, 2020, 26(4): 2143-2151. DOI: 10.1007/s12253-020-00799-y.
    [20]
    SCHROEDER B, MCNIVEN MA. Importance of endocytic pathways in liver function and disease[J]. Compr Physiol, 2014, 4(4): 1403-1417. DOI: 10.1002/cphy.c140001.
    [21]
    WANG HX, LIU M, WENG SY, et al. Immune mechanisms of Concanavalin A model of autoimmune hepatitis[J]. World J Gastroenterol, 2012, 18(2): 119-125. DOI: 10.3748/wjg.v18.i2.119.
    [22]
    HONG L, CAI Y, JIANG M, et al. The Hippo signaling pathway in liver regeneration and tumorigenesis[J]. Acta Biochim Biophys Sin (Shanghai), 2015, 47(1): 46-52. DOI: 10.1093/abbs/gmu106.
    [23]
    MOHSENI R, KARIMI J, TAVILANI H, et al. Carvacrol ameliorates the progression of liver fibrosis through targeting of Hippo and TGF-β signaling pathways in carbon tetrachloride (CCl4)-induced liver fibrosis in rats[J]. Immunopharmacol Immunotoxicol, 2019, 41(1): 163-171. DOI: 10.1080/08923973.2019.1566926.
    [24]
    SUI M, JIANG X, CHEN J, et al. Magnesium isoglycyrrhizinate ameliorates liver fibrosis and hepatic stellate cell activation by regulating ferroptosis signaling pathway[J]. Biomed Pharmacother, 2018, 106: 125-133. DOI: 10.1016/j.biopha.2018.06.060.
    [25]
    KONG Z, LIU R, CHENG Y. Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway[J]. Biomed Pharmacother, 2019, 109: 2043-2053. DOI: 10.1016/j.biopha.2018.11.030.
    [26]
    LYBEROPOULOU A, CHACHAMI G, GATSELIS NK, et al. Low serum hepcidin in patients with autoimmune liver diseases[J]. PLoS One, 2015, 10(8): e0135486. DOI: 10.1371/journal.pone.0135486.
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